Ignite Creation Date:
2024-05-06 @ 9:39 AM
Last Modification Date:
2024-10-26 @ 12:17 PM
Study NCT ID:
NCT03031730
Status:
TERMINATED
Last Update Posted:
2024-07-03
First Post:
2017-01-25
Brief Title:
Testing the Addition of KRT-232 AMG 232 to Usual Chemotherapy for Relapsed Multiple Myeloma
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase 1 Dose-Escalation and Exploratory Dose Expansion Study of KRT-232 AMG 232 in Combination With Carfilzomib Lenalidomide and Dexamethasone in Relapsed andor Refractory Myeloma
Status:
TERMINATED
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Inadequate accrual rate
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial studies the side effects and best dose of MDM2 Inhibitor KRT-232 when given together with carfilzomib lenalidomide and dexamethasone in treating patient with multiple myeloma that has come back relapsed or has not responded to previous treatment refractory KRT-232 AMG 232 may stop the growth of cancer cells by blocking a protein called MDM2 that is needed for cell growth Lenalidomide help shrink or slow the growth of multiple myeloma Drugs used in chemotherapy such as carfilzomib and dexamethasone work in different ways to stop the growth of cancer cells either by killing the cells by stopping them from dividing or by stopping them from spreading Giving MDM2 Inhibitor KRT-232 lenalidomide carfilzomib and dexamethasone together may work better in treating patients with multiple myeloma
Detailed Description:
PRIMARY OBJECTIVES
I Evaluate safety and tolerability of MDM2 Inhibitor KRT-232 KRT-232 AMG 232 in combination with carfilzomib lenalidomide and dexamethasone KRd Part A II Determine the maximum tolerated dose MTD and recommended phase 2 dose RP2D of KRT-232 AMG 232 in combination with carfilzomib lenalidomide and dexamethasone KRd Part A III Confirm the safety and tolerability of KRT-232 AMG 232 in combination with carfilzomib lenalidomide and dexamethasone KRd at MTDtentative RP2D in a goal of 10 subjects with relapsed andor refractory myeloma Part B
SECONDARY OBJECTIVES
I Evaluate progressive disease PD effects of KRT-232 AMG 232 through serum MIC-1 levels Part A II Assess KRT-232 AMG 232 exposure-response relationships PD toxicity and efficacy Part A III Evaluate the overall response rate of KRT-232 AMG 232 in combination with carfilzomib lenalidomide and dexamethasone KRd in relapsedrefractory myeloma by International Myeloma Working Group IMWG criteria Part B IV Evaluate PD effects of KRT-232 AMG 232 through serum MIC-1 levels Part B V Assess KRT-232 AMG 232 exposure-response relationships PD toxicity and efficacy Part B
EXPLORATORY OBJECTIVES
I To observe and record anti-tumor activity of KRT-232 AMG 232 in combination with carfilzomib lenalidomide and dexamethasone KRd in relapsedrefractory myeloma by International Myeloma Working Group IMWG criteria Part A II Evaluate ribonucleic acid RNA expression levels of relevant genes in the TP53 pathway that may predict response to therapy using pre- and post-treatment bone marrow biopsies Parts A and B
OUTLINE This is a dose-escalation study of MDM2 Inhibitor KRT-232
Patients receive MDM2 Inhibitor KRT-232 orally PO once daily QD on days 1-7 carfilzomib intravenously IV over 10-30 minutes on days 1-2 8-9 and 15-16 of cycles 1-12 and on days 1-2 and 15-16 of cycles 13-18 lenalidomide PO on days 1-21 and dexamethasone PO or dexamethasone sodium phosphate IV on days 1 8 15 and 22 Cycles repeat every 28 days in the absence of disease progression or unexpected toxicity Patients undergo echocardiography during screening and bone marrow biopsy and aspiration and blood sample collection throughout the study
After completion of study treatment patients are followed up for 30 days
I Evaluate safety and tolerability of MDM2 Inhibitor KRT-232 KRT-232 AMG 232 in combination with carfilzomib lenalidomide and dexamethasone KRd Part A II Determine the maximum tolerated dose MTD and recommended phase 2 dose RP2D of KRT-232 AMG 232 in combination with carfilzomib lenalidomide and dexamethasone KRd Part A III Confirm the safety and tolerability of KRT-232 AMG 232 in combination with carfilzomib lenalidomide and dexamethasone KRd at MTDtentative RP2D in a goal of 10 subjects with relapsed andor refractory myeloma Part B
SECONDARY OBJECTIVES
I Evaluate progressive disease PD effects of KRT-232 AMG 232 through serum MIC-1 levels Part A II Assess KRT-232 AMG 232 exposure-response relationships PD toxicity and efficacy Part A III Evaluate the overall response rate of KRT-232 AMG 232 in combination with carfilzomib lenalidomide and dexamethasone KRd in relapsedrefractory myeloma by International Myeloma Working Group IMWG criteria Part B IV Evaluate PD effects of KRT-232 AMG 232 through serum MIC-1 levels Part B V Assess KRT-232 AMG 232 exposure-response relationships PD toxicity and efficacy Part B
EXPLORATORY OBJECTIVES
I To observe and record anti-tumor activity of KRT-232 AMG 232 in combination with carfilzomib lenalidomide and dexamethasone KRd in relapsedrefractory myeloma by International Myeloma Working Group IMWG criteria Part A II Evaluate ribonucleic acid RNA expression levels of relevant genes in the TP53 pathway that may predict response to therapy using pre- and post-treatment bone marrow biopsies Parts A and B
OUTLINE This is a dose-escalation study of MDM2 Inhibitor KRT-232
Patients receive MDM2 Inhibitor KRT-232 orally PO once daily QD on days 1-7 carfilzomib intravenously IV over 10-30 minutes on days 1-2 8-9 and 15-16 of cycles 1-12 and on days 1-2 and 15-16 of cycles 13-18 lenalidomide PO on days 1-21 and dexamethasone PO or dexamethasone sodium phosphate IV on days 1 8 15 and 22 Cycles repeat every 28 days in the absence of disease progression or unexpected toxicity Patients undergo echocardiography during screening and bone marrow biopsy and aspiration and blood sample collection throughout the study
After completion of study treatment patients are followed up for 30 days
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| UM1CA186688 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186688 |
| NCI-2017-00099 | REGISTRY | None | None |
| NCI10076 | None | None | None |
| 10076 | OTHER | None | None |
| 10076 | OTHER | None | None |